| Autor: |
Baldini E; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Cardarelli S; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Campese AF; Department of Molecular Medicine, 'Sapienza' University of Rome, 00161 Rome, Italy., Lori E; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Fallahi P; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy., Virili C; Department of Medico-Surgical Sciences and Biotechnologies, 'Sapienza' University of Rome, 04100 Latina, Italy., Forte F; Department of Urology, M.G. Vannini Hospital, 00177 Rome, Italy., Pironi D; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Di Matteo FM; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Palumbo P; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Costanzo ML; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., D'Andrea V; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Centanni M; Department of Medico-Surgical Sciences and Biotechnologies, 'Sapienza' University of Rome, 04100 Latina, Italy., Sorrenti S; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy., Antonelli A; Department of Surgical, Medical and Molecular Pathology and of Critical Area, University of Pisa, 56126 Pisa, Italy., Ulisse S; Department of Surgery, 'Sapienza' University of Rome, 00161 Rome, Italy. |
| Abstrakt: |
Anaplastic thyroid carcinoma (ATC) is an extremely difficult disease to tackle, with an overall patient survival of only a few months. The currently used therapeutic drugs, such as kinase inhibitors or immune checkpoint inhibitors, can prolong patient survival but fail to eradicate the tumor. In addition, the onset of drug resistance and adverse side-effects over time drastically reduce the chances of treatment. We recently showed that Twist1, a transcription factor involved in the epithelial mesenchymal transition (EMT), was strongly upregulated in ATC, and we wondered whether it might represent a therapeutic target in ATC patients. To investigate this hypothesis, the effects of harmine, a β-carboline alkaloid shown to induce degradation of the Twist1 protein and to possess antitumoral activity in different cancer types, were evaluated on two ATC-derived cell lines, BHT-101 and CAL-62. The results obtained demonstrated that, in both cell lines, harmine reduced the level of Twist1 protein and reverted the EMT, as suggested by the augmentation of E-cadherin and decrease in fibronectin expression. The drug also inhibited cell proliferation and migration in a dose-dependent manner and significantly reduced the anchorage-independent growth of both ATC cell lines. Harmine was also capable of inducing apoptosis in BHT-101 cells, but not in CAL-62 ones. Finally, the activation of PI3K/Akt signaling, but not that of the MAPK, was drastically reduced in treated cells. Overall, these in vitro data suggest that harmine could represent a new therapeutic option for ATC treatment. |
